Dynamics of the Cellular Metabolome during Human Cytomegalovirus Infection

PLoS Pathogens

Sunil U Bajad¹  Joshua D Rabinowitz¹  Joshua Munger²  Thomas Shenk²  Hilary A Coller² 

[1] Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America;Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America

关键词: Cell metabolism;    Metabolites;    Enzyme metabolism;    Fibroblasts;    Cytomegalovirus infection;    Human cytomegalovirus;    Metabolic pathways;    Pyruvate;   

DOI  :  10.1371/journal.ppat.0020132

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. Despite this reliance, the effect of viral infection on host cell metabolic composition remains poorly understood. Here we applied liquid chromatography-tandem mass spectrometry to measure the levels of 63 different intracellular metabolites at multiple times after human cytomegalovirus (HCMV) infection of human fibroblasts. Parallel microarray analysis provided complementary data on transcriptional regulation of metabolic pathways. As the infection progressed, the levels of metabolites involved in glycolysis, the citric acid cycle, and pyrimidine nucleotide biosynthesis markedly increased. HCMV-induced transcriptional upregulation of specific glycolytic and citric acid cycle enzymes mirrored the increases in metabolite levels. The peak levels of numerous metabolites during infection far exceeded those observed during normal fibroblast growth or quiescence, demonstrating that HCMV markedly disrupts cellular metabolic homeostasis and institutes its own specific metabolic program.

【 授权许可】

CC BY